1. Field of the Invention
The present invention relates to a simple method for preparing a quinolinone derivative, which is effective as a medicine, e.g., as an agent for treating allergic diseases and the like; novel amide derivatives effective as an intermediate in said method; novel quinolinone derivatives obtained by means of said method; and an anti-allergic agent containing a quinolinone derivative and/or physiological salt of the same as the active ingredients.
2. Background Art
The inventors of the present invention have found that a quinolinone derivative having a substituent group at the 7-position and physiological salts thereof are effective against both immediate-type hypersensitivity reactions and delayed-type hypersensitivity reactions, being extremely useful as a drug with few side effects, as disclosed in Japanese Patent Application, First Application No. Hei 09-100267 and Japanese Patent Application, First Application No. Hei 09-255659. A method for preparing such a quinolinone derivative was disclosed in both Japanese Patent Application, First Application No. Hei 09-100267 and Japanese Patent Application, First Application No. Hei 09-255659, as shown below. ##STR3## ##STR4##
However, in the preparation method disclosed in these documents, in particular, when preparing a compound having a substituent group at the 3-position, it was necessary to proceed along a complex reaction pathway involving the steps of introducing a protecting group, de-protecting, introducing a substituent group, and then de-protecting again. Thus, the method was not necessarily satisfactory for industrial application.
Examples of other quinolinone derivatives and methods for preparing the same, include Monatsh. Chem., 98(1), pp. 100-104, 1967, which discloses infrared absorption spectrum data for 3-methoxy-4-hydroxy-2(1H)-quinolinone, 3-ethoxy-4-hydroxy-2(1H)-quinolinone, and 3,4-dimethoxy-2(1H)-quinolinone, as quinolinone compounds having substituent groups at the 3- and 4-positions of the nitrogen-containing ring of quinolinone, while lacking substituent groups on the aromatic group ring.
Monatsh. Chem., 99(6), pp. 2157-2166, 1968, also discloses a method for preparing 3,4-dihydroxy-2(1H)-quinolinone and 3,4dihydroxy-1-phenyl-2(1H)-quinolinone.
Additionally, Liebigs Ann. Chem., 9, pp. 1545-1551, 1973, discloses a method for preparing 3,4-dihydroxy-1-phenyl-2(1H)-quinolinone and 3,4-diacetoxy-1-phenyl-2(1H)-quinolinone.
Furthermore, Chem. Ber. 106, pp. 1537-1548, 1973, discloses a method for preparing 3,4-dihydroxy-1-methyl-2(1H)-quinolinone, and Z. Naturforsch., B; Anorg. Chem., Org. Chem., 33B (4) pp. 429-432, 1978, discloses a method for preparing 3,4-dihydroxy-1-phenyl-2(1H)-quinolinone.
Monatsh. Chem., 115(2), pp. 231-242, 1984, discloses a method for preparing 3,4-dihydroxy-2(1H)-quinolinone, 3-methoxy4-hydroxy-2(1H)-quinolinone, 3-ethoxy-4-hydroxy-2(1H)-quinolinone, 3-propoxy-4-hydroxy-2(1H)-quinolinone, 3-trifluoroacetoxy-4-hydroxy-2(1H)-quinolinone, 3-acetoxy-4-hydroxy-2(1H)-quinolinone, 3-acetoxy-4-hydroxy-1-methyl-2(1H)-quinolinone, and 3-methoxy-4-hydroxy-1-methyl-2(1H)-quinolinone.
Phosphorus and Sulfur, 21(1), pp. 47-52, 1984, discloses 3,4-dihydroxy-2(1H)-quinolinone 3-dimethylphosphate, 3-hydroxy-4-methoxy-2(1H)-quinolinone 3-dimethylphosphate, 3,4-dihydroxy-2(1H)-quinolinone 3-diethylphosphate, 3,4-dihydroxy-2(1H)-quinolinone 3-diisopropylphosphate, and N-methyls of these compounds.
FEBS Lett., 246(1-2), pp. 113-116, 1989, discloses a method for preparing 3,4-dihydroxy-2(1H)-quinolinone. Phytochemistry, 28(5), pp. 1517-1519, 1989, discloses 3,4-dimethoxy-2(1H)-quinolinone and 3,4-dimethoxy-1-methyl-2(1H)-quinolinone as extracts of Clausena anisata.
As compounds having substituent groups on the aromatic ring of a quinolinone, Indian J. Chem., Sect. B, 15B(5), pp. 440-444, 1977, discloses 3,4-dimethoxy-2(1H)-quinolinone, 8-methoxy-3-methoxy-4-hydroxy-1-methyl-2(1H)-quinolinone, and a methyl ether thereof, 8-methoxy-3,4-dimethoxy-1-methyl-2(1H)-quinolinone as compounds obtained from the bark of Chloroxylon swietenia DC.
Additionally, Indian J. Chem., Sect. B, 22B(12), pp. 1254-1256, 1983, discloses a method for preparing 8-methoxy-3-methoxy-4-hydroxy-2(1H)-quinolinone and 8-methoxy-3,4-dimethoxy-1-methyl-2(1H)-quinolinone.
Additionally, J. Heterocyclic Chem., 22, pp. 1087-1088, 1985, discloses a method for preparing 3-methoxy-4-hydroxy-1-methyl-2(1H)-quinolinone and 8-methoxy-3-methoxy-4-hydroxy-1-methyl-2(1H)-quinolinone.
Journal of Natural Products, 58(4), pp. 574-576, 1995, discloses 8-methoxy-3,4-dihydroxy-2(1H)-quinolinone as a component obtained from Eriostemon gardneri. However, as described above, only methoxy groups are known as substituent groups for the aromatic group rings of quinolinone derivatives.
In addition, U.S. Pat. No. 5,378,694 (corresponding to WO 92/04328 and Japanese Patent Application, Second Publication No. Hei 6-502845) describes quinolinone derivatives having a carbonyl group as the 3-position substituent group, and a hydroxyl group or an alkoxy group as the 4-position substituent group; the anti-viral activities and anti-hypertensive activities of these compounds are also described therein.
Moreover, U.S. Pat. No. 5,412,104 (corresponding to WO 92/04327 and Japanese Patent Application, Second Publication No. Hei 7-110853) describes quinolinone derivatives having a substituent group containing a carbonyl group as the 3-position substituent group, and an alkoxy group, a carbonyloxy group or an amino group as the 4-position substituent group, along with the anti-viral activities of these compounds; European Patent No. 0459561 A2 discloses 2,4-dioxotetrahydroquinoline derivatives, wherein the 3-position substituent group is a substituent group containing a carbonyl group and the 4-position group is a 4-ketone tautomer.
European Patent Application, Publication No. 0481676 A1 discloses a quinolinone derivative having an aromatic group with a substituent group as the 3-position substituent group and a hydroxyl group as the 4-position substituent group; U.S. Pat. No. 4,124,587 discloses a quinolinone derivative having a sulfinyl group as the 3-position substituent group and a hydroxyl group as the 4-position substituent group; and U.S. Pat. No. 4,127,574 discloses a quinolinone derivative having a sulfonyl group as the 3-position substituent group and a hydroxyl group as the 4-position substituent group.
WO 96/04288 discloses 5,7-dimethyl-4-hydroxy-2(1H)-quinolinone and 5,7-dichloro-4-hydroxy-2(1H)-quinolinone; Furthermore, U.S. Pat. No. 5,179,107 and U.S. Pat. No. 5,190,956 abstractly describe an extremely wide range of quinolinone derivatives having substituent groups on the aromatic group ring and having oxygens directly bonded to the 3- and 4-positions.
These US patent publications disclose quinolinone derivatives having the characteristic that the substituent groups at the 3- and 4-positions are identical substituent groups, and disclose that these derivatives have anti-viral activity.